HIV-1 infected subjects treated with an autologous dendritic cell therapy (AGS-004), exhibited a significant reduction in viral load (when compared to pre-ART viral load) and delay in the time to viral rebound during a 12

week structured treatment interruption (STI)

J.P. Routy1, J. Angel2, S. Vezina3, C. Tremblay4, M. Loutfy5, J. Gill6, J.-G. Baril7, F. Smaill8, R. G. Jain9, I. Y. Tcherepanova9, M.-R. Boulassel10, T. Monesmith9, R. P. Sekaly11, C. A. Nicolette9,

and AGS 004-001 Study Group1McGill University Health Centre, INSERM Unit 743, Montréal, Canada, 2Ottawa Hospital, Ottawa, Canada, 3Clinique Médicale l'Actuel,

Montréal, Canada, 4Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada, 5Maple Leaf Clinic, Toronto, Canada, 6Southern Alberta Clinic, Calgary, Canada, 7Clinique Medicale du Quartier Latin, Montréal, Canada, 8Hamilton Health Sciences - McMaster University Medical Centre, Hamilton, Canada, 9Argos Therapeutics Inc, Durham NC, United States, 10McGill University Health

Centre, Montréal, Canada, 11University of Montréal Research Centre, Montréal, Canada

Funded by NIAID, NIH (NO1-A1-60019), CTN-CIHR #239 and Argos Therapeutics,

Inc.

Background and rationale

• ART represents a major breakthrough for the management of HIV-infected patients, however is not without side effects and is a life long commitment

• Therapeutic vaccines to enhance immune response and control viral replication are needed to limit exposure to ART

• AGS-004, (Argos Therapeutics) which consists of autologous monocyte-derived dendritic cells co-electroporated with in vitro transcribed RNA encoding four of the patient’s own HIV antigens (Gag, Vpr, Rev, and Nef) was developed

• A phase 1 study demonstrated CTL induction without activating CD4+ T cells (Routy et al. Clin Immunol 2010)

Study Design: Phase 2

AGS-004 dosing every 4 weeks8 weeks 12 weeks

ART 12 Week STI Booster Phase ART

Study design: Single-arm, open-label, multicenter, Phase 2 study to assess safety and antiviral activity of AGS-004

4 doses of AGS-004 while on ART, 2 doses off ART and then dosed when VL< 10 000 copies/ml

End points: Time to VL rebound, Pre-ART vs. Wk 12 of STI change in VL, tolerance, restart ART when CD4 < 350 /mm3

Key Criteria: First ART with VL <50 copies/ml, CD4 ≥450/mm3 for at least 90 days, nadir ≥200/mm3

Booster phase if VL < 10 000 copies/ml

Time from ART Interruption to Viral Load Rebound, n=22

0 1 2 3 4 5 6 7 8 9 10

Time to Detectable Viral Load (≥50 HIV-1 RNA copies/mL) in Weeks

Median time to viral load rebound

(≥50 copies/mL) = 3.86 weeksMean time: 3.77 weeks

• 22 Patients out of 29 who received AGS-004 immunotherapy: Interim analysis

• Blood sampling q 2 weeks• Increase in the proportion of patients with VL rebound ≥ day 14 was seen

from historical control. Swiss cohort, Fischer et al. AIDS 2003; 17; 195• Fisher’s exact test, the p-value for the difference = 0.006

• The median reduction for responders (n=14) was -0.82 log• No association between the change in viral load and susceptible (B*31,

B*45, B*35) or protective (B*27, B*51, B*57) HLA alleles        

Pre-ART vs. Week 12 of STI Log Change in Viral LoadN=22

-6.00

-5.00

-4.00

-3.00

-2.00

-1.00

0.00

1.00

2.00

Log C

hange in V

iral Lo

ad

Mean reduction in viral load -0.72 log (n=22)

For those who had lower VL than pre-ART(n=14)Mean reduction in viral load = -1.30 log

Conclusion

• Administration of AGS-004 immunotherapy:• Feasible in a multicenter study• Safe, with no additional risk observed during STI• Long delay in viral rebound• Lower viral load when compared to pre-ART levels

• CD4 T cell counts:• No significant decrease from the median of the last three CD4+ T

cell counts on ART vs. in the STI (p-value = 0.20)

• Immune correlate: – CD8 T-cells was consistent with an effector/memory response– Absence of CD4 induced activation– Poster THPE0181, C Nicolette

• These results warrant further evaluation: – Phase 2 b, NIH-supported double-blind, placebo-controlled,

randomized study, AGS-004-003 in US and Canada